Benzathine penicillin G is the treatment of choice for infectious syphilis, but tetracycline and doxycycline are believed to be effective second-line treatments. The objective of this study was to assess the serological response from treatment of primary syphilis with benzathine penicillin compared with doxycycline or tetracycline.

We examined rapid plasma reagin serological test results of all first-time primary syphilis patients in Alberta, Canada from 1980 to 2001 and compared treatment with single dose of penicillin with 14-day course of oral doxycycline (100 mg twice a day) or oral tetracycline (500 mg 4 times a day). Serological treatment success was defined as a minimum 4-fold decrease in baseline rapid plasma reagin test antibody titer within 6 months, or ≥8-fold decrease within 12 months, or ≥16-fold decrease by 24 months. The median time to successful response was estimated, and factors associated with treatment success were identified by unadjusted logistic regression.

Of the 445 primary syphilis cases with available treatment outcome data, 420 (94.4%) received penicillin and 25 (5.6%) received doxycycline/tetracycline. The serological treatment success rate was 97.4% in the penicillin group (409/420) and 100% in the doxycycline/tetracycline group (25/25), and not significantly different. The estimated median time to serological treatment success was 72.0 days (mean=101.7, range 10-603) in penicillin and 43.0 days (mean=78.6, range 15-334) in doxycycline/tetracycline-treated patients; however, this difference was not statistically significant (P=0.16).

Doxycycline/tetracycline had a similarly high serological treatment success rate when compared with penicillin in the treatment of primary syphilis.